The present invention is drawn to a process of producing azalide antibiotics which are useful in the therapy of bacterial infections in mammals.
Modifications of the western fragment of erythromycin A have been difficult to obtain. There is a long felt need for new azalide antibiotics, and in particular, for a process of varying the western fragment of such azalides. The invention thus provides a process of making azalide compounds with modified western fragments.
Erythromycin A has been the subject of investigation for many years. Erythromycin A has the following structural formula: ##STR1##
Reactions can be conducted which lead to rupture of the ring and formation of the C.sub.1 carboxylate. This reaction can generally be conducted as follows: ##STR2##
The present invention utilizes the fragments above, as well as other eastern fragments to produce novel 8a- and 9a- azalides. By modifying these fragments to produce 8a- and 9a- aza fragments, and combining the modified eastern fragments or derivatives thereof with an appropriate compound which forms the western portion of the molecule, the azalide ring structure can be formed. Thus, a large number of azalides can now be produced with modifications in the western portion of the molecule.